Pharmaceutical solid preparations are sometimes film coated for the purpose of reducing side effects, decreasing the administration frequency, masking the bitter taste of a drug, etc. The film coating is applicable to a tablet and a granular agent but is often applied to granular agents to reduce the unevenness of the coating film. In particular, since the drug dissolution rate must be precisely controlled, spherical core particles having a uniform particle size are commonly used. Further, the most preferred dosage form in the pharmaceutical solid preparations by patients is a tablet, thus it is desired that other excipients be added to the film-coated granule to form a tablet. Furthermore, to enhance the patient compliance, a preparation formulated into a quick-disintegrating tablet in the buccal cavity which can be taken without water is even more desirable.
The common technology for producing a tablet is the compression molding using a tableting machine. In order to assure the practical productivity, handleability and transportability of tablets, the tablet hardness must be increased by compression-molding with a certain level of pressure. However, this pressure often damages the film of the film-coated granules, causing the loss of the drug dissolution functions and the loss of masking effect on the bitter taste of a drug. Thus, the coating with a plurality of films, and the like, have been attempted.
It is very advantageous in terms of productivity to complete a film coating step using one kind of film. A method that allows a film to withstand mechanical stress during tableting is to impart the film with the flexibility like rubber. However, a highly flexible film also has a highly tacky film surface, likely causing granules to agglomerate during the film coating. To prevent the granule agglomeration during the film coating, there are counteractive techniques such as using large granules, reducing the coating rate of a film coating liquid, and adding a tackiness-reducing agent such as talc to a film coating liquid. However, it is conventionally difficult to cope with various sizes of granules without sacrificing the productivity and film properties (drug dissolution control, masking control of the bitter taste of a drug and mechanical strengths).
It is known that a film made from an ethyl acrylate/methyl methacrylate copolymer and a vinyl acetate polymer is very flexible. However, such a film has a highly tacky surface and thus practical film coating has been difficult unless a tackiness-reducing agent such as talc is added. In particular, the film coating of granules having an average particle size of 300 μm or less has been extremely difficult.
In recent years, as the society is rapidly aging, quick-disintegrating tablets in the buccal cavity which quickly disintegrates in saliva or in a small amount of water have been developed as the dosage form easily taken even by elderly and pediatric patients who have weak swallowing ability. Such a tablet has been contributing to enhanced convenience at medical practice sites and the patient compliance through ease of administration. However, the quick-disintegrating tablet in the buccal cavity has short history, and there are technical problems such as disintegrating time and mouthfeel in the buccal cavity and assuring the tablet hardness free from cracks and abrasion during the production and transportation. Consequently, it is demanded to develop technology for producing a quick-disintegrating tablet in the buccal cavity which has a suitable hardness, quick-disintegrating properties and enhanced mouthfeel by masking the bitter taste of a drug. Even higher achievement in the technology for producing a quick-disintegrating tablet in the buccal cavity is expected.
Patent Literature 1 discloses the film coating agent for a granule-containing tablet having sustained-release properties which gradually release a drug, but not for the purpose of masking the bitter taste of a drug.
Patent Literature 2 describes a quick-disintegrating tablet in the buccal cavity in which the bitter taste of a drug is masked. However, the method described in the literature is to produce a bitterness-masked drug-containing particle without coating a microcrystalline cellulose core particle with a drug, but by mixing a film coating liquid to a drug and a saccharide and then spray drying the obtained mixture. Further, Patent Literature 2 discloses a method for producing a tablet by mixing the resultant drug-containing particle and a saccharide.
Patent Literature 3 discloses a method for preventing the film damage caused during tableting by allowing a carbohydrate core particle to carry a drug and coating the particle with at least two film layers.
Patent Literature 4 discloses a method for producing a film-coated granule which releases a drug in a short time by allowing a spherical core particle to carry a drug and coating the particle with the film to mask the bitter taste.